Question about the biology of Test/DHT/5AR

[revolt]

When 5ARII enzyme converts Test to DHT, what exactly occurs?

1) Does the 5ARII enzyme "bond" to the testosterone, which becomes DHT. DHT is thus essentially a combination of 5ARII + TEST. Then there is no more 5ARII enzyme until the body produces more...

OR

2) Does the 5ARII enzyme attach to the testosterone, and after it works its "magic," it releases the testosterone in its new transformed state, DHT. The enzyme then doesn't go away, but is always present and continues to convert test to DHT on a perpetual basis. It works like a filter in this case (testosterone "passes through" the 5ARII enzyme and becomes DHT, and the 5ARII is always present).

Or does it work in some other way??

 

[Bryan]

Your second explanation is much closer to the truth: the 5a-reductase type 1 and type 2 enzymes are tightly bound to internal cellular membranes; when a molecule of testosterone in the cytoplasm of the cell encounters them, it's chemically converted into a molecule of DHT, with the help of yet another chemical called NADPH, which is required for that conversion. Afterwards, the molecule of DHT by itself is free to bind to androgen receptors in the cytoplasm and/or the nucleus of the cell.

The one thing I'll add here that I'm a little vague about is that the cell regularly makes "fresh" 5a-reductase enzymes, so I'm assuming that there's a fairly regular turnover of that enzyme. Whether or not the enzyme gets destroyed by being irreversibly bound to drugs like finasteride and dutasteride, I assume that it gets replaced on a regular basis.

 

[revolt]

Thanks Bryan... been doing some more research on enzymes and its making a bit more sense to me.

One thing I was reading about was the rates at which enzymes convert the substrate to the product as well as when an enzyme becomes saturated... so when 5AR becomes saturated because there are such high levels of the substrate (testosterone), you're going to get the maximum amount of DHT produced. Even if you increase testosterone, DHT won't increase because the enzyme is saturated (maxed out).

So its interesting... if finasteride inhibits most of the 5ARII enzymes, you would assume the few remaining enzymes would become saturated (or closer to it) because the ratio of test to 5ARII has now increased dramatically.

In practice though, do the remaining enzymes normally become saturated with finasteride use?

 

[Bryan]

So its interesting... if finasteride inhibits most of the 5ARII enzymes, you would assume the few remaining enzymes would become saturated (or closer to it) because the ratio of test to 5ARII has now increased dramatically.

In practice though, do the remaining enzymes normally become saturated with finasteride use?

Seems like a pretty safe bet, doesn't it?